TY - JOUR T1 - Microarray analysis identifies defect in regenerative and immune response pathways in COPD airway basal cells JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00656-2020 SP - 00656-2020 AU - Fanny Pineau AU - Gabriella Shumyatsky AU - Nicole Owuor AU - Nisha Nalamala AU - Sudhir Kotnala AU - Sudhir Bolla AU - Nathaniel Marchetti AU - Steven Kelsen AU - Gerard J. Criner AU - Uma S. Sajjan Y1 - 2020/01/01 UR - http://openres.ersjournals.com/content/early/2020/09/17/23120541.00656-2020.abstract N2 - Background Airway basal cells are specialised stem cells and regenerate airway epithelium. Airway basal cells isolated from patients with chronic obstructive pulmonary disease (COPD) regenerate airway epithelium with an abnormal phenotype. We performed gene expression analysis to gain insights into the defective regenerative program in COPD basal cells.Methods We conducted microarray analysis and compared COPD versus normal basal cells to identify differentially regulated genes (DEG) and the enriched biological pathways. We determined the correlation of DEG with cell polarisation and markers of ciliated and goblet cells. HOXB2 was knocked down in 16HBE14o- cells and monitored for polarisation of cells. HOXB2 expression in the lung sections was determined by immunofluorescence.Results Comparison of normal and COPD basal cell transcriptomic profiles highlighted downregulation of genes associated with tissue development, epithelial cell differentiation and antimicrobial humoral response. Expression of one of the tissue development genes, HOXB2 showed strong correlation with transepithelial resistance and this gene was downregulated in COPD basal cells. Knockdown of HOXB2, abrogated polarisation of epithelial cells in normal cells. Finally, HOXB2 expression was substantially reduced in the bronchial epithelium of COPD patients.Conclusions Defect in gene signatures involved in tissue development and epithelial differentiation were implicated in COPD basal cells. One of the tissue developmental genes, HOXB2, is substantially reduced in bronchial epithelium of COPD patients. Since HOXB2 contributes to airway epithelial cell polarisation, we speculate that reduced expression of HOXB2 in COPD may contribute to abnormal airway epithelial regeneration in COPD.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Pineau has nothing to disclose.Conflict of interest: Dr. Pineau has nothing to disclose.Conflict of interest: Dr. Pineau has nothing to disclose.Conflict of interest: Dr. Pineau has nothing to disclose.Conflict of interest: Dr. Pineau has nothing to disclose.Conflict of interest: Sudhir BollaConflict of interest: Dr. Marchetti has nothing to disclose.Conflict of interest: Dr. Kelsen has nothing to disclose.Conflict of interest: Dr. Criner has nothing to disclose.Conflict of interest: Dr. Pineau has nothing to disclose. ER -